Robbins Flashcards
(144 cards)
1
Q
Blood cell progenitors first appear during the third week of embryonic development in the
A
yolk sac
2
Q
Cells derived from the _____ are the source of long-lived tissue macrophages such as microglial cells in the brain and Kupffer cells in the liver
A
yolk sac
3
Q
During the third month of embryogenesis, HSCs migrate to the ______, which becomes the chief site of blood cell formation until shortly before birth
A
liver
4
Q
By birth, _____ hematopoietically active, and hepatic hematopoiesis dwindles to a trickle, persisting only in scattered foci that become inactive soon after birth.
A
bone marrow
5
Q
T/F After puberty, hematopoiesis continuous throughout the entire skeleton.
A
False:
After puberty, hematopoiesis ceases in distal bones and becomes restricted to the axial skeleton.
6
Q
refers to the ability of a single hematopoietic stem cell (HSC) to generate all mature blood cells.
A
Pluripotency
7
Q
T/F In adulthood, HSCs are immobile and remain in the bone marrow
A
False
Under conditions of stress, such as severe anemia or acute inflammation, HSCs are mobilized from the bone marrow and appear in the peripheral blood
8
Q
some divisions of HSCs give rise to cells referred to as ________, which are more proliferative than HSCs but have a lesser capacity for self-renewal
A
multipotent progenitors
9
Q
T/F In acute viral infections, lymphopenia stems from an overall decrease in the number of lymphocytes in the body
A
False
In acute viral infections, lymphopenia actually stems from lymphocyte redistribution (sequestration of activated T cells in lymph nodes and increased adherence to endothelial cells)
10
Q
2 causes of neutropenia
A
inadequate or ineffective granulopoiesis
increased destruction or sequestration of neutrophils in the periphery
11
Q
The most common cause of agranulocytosis is
A
drug toxicity
12
Q
mechanisms of leukocytosis (4)
A
Increased Marrow Production
Increased Release From Marrow Stores
Decreased Margination
Decreased Extravasation Into Tissues
13
Q
T/F exercise may cause leukocytosis as it decreases margination
A
True
14
Q
In _________ leukocytosis is often accompanied by morphologic changes in neutrophils, such as toxic granulations, Döhle bodies, and cytoplasmic vacuoles
A
sepsis or severe inflammatory disorders
15
Q
This morpholigic change in neutrophils called______ are coarser and darker than normal neutrophilic granules and represent abnormal azurophilic (primary) granules
A
toxic granules
16
Q
This morpholigic change in neutrophils called ____ are patches of dilated endoplasmic reticulum that appear as sky-blue cytoplasmic “puddles.”
A
Döhle bodies
17
Q
hyperplasia caused by stimuli that activate humoral immune responses. It is defined by the presence of large oblong germinal centers (secondary follicles), which are surrounded by a collar of small resting naive B cells (the mantle zone)
A
follicular hyperplasia
18
Q
macrophages in the germinal centers containing the nuclear debris of B cells are called
A
tingible-body macrophages
19
Q
When do B cells in the germinal centers undergo apoptosis?
A
B cells in the germinal centers undergo apoptosis if they fail to produce an antibody with a high affinity for the presented antigen
20
Q
Features favoring a reactive follicular (nonneoplastic) hyperplasia (3)
A
- preservation of the lymph node architecture, including the interfollicular T-cell zones and the sinusoids
- marked variation in the shape and size of the follicles
- presence of frequent mitotic figures, phagocytic macrophages, and recognizable light and dark zones, all of which tend to be absent from neoplastic follicles
21
Q
hyperplasia caused by stimuli that trigger T-cell–mediated immune responses, such as acute viral infections
A
Paracortical hyperplasia
22
Q
is marked by an increase in the number and size of the endothelial cells that line lymphatic sinusoids and increased numbers of intrasinusoidal macrophages, which expand and distort the sinusoids
A
Sinus histiocytosis
23
Q
Three lymphotropic viruses implicated as causative agents in particular lymphomas
A
HTLV-1
EBV
HHV-8
24
Q
World Health Organization (WHO) classification scheme uses morphologic, immunophenotypic, genotypic, and clinical features to sort the lymphoid neoplasms into five broad categories namely
A
- Precursor B-cell neoplasms
- PeripheralB-cellneoplasms
- Precursor T-cell neoplasms
- Peripheral T-cell and NK-cell neoplasms
- Hodgkin lymphomas
25
T/F Lymphoid neoplasia can be diagnosed based on clinical features
False
Lymphoid neoplasia can be suspected based on clinical features, but histologic examination of lymph nodes or other involved tissues is required for diagnosis
26
T/F all daughter cells derived from the malignant progenitor share the same antigen receptor gene configuration and sequence and synthesize identical antigen receptor proteins
true
27
T/F vast majority of lymphoid neoplasms are of B-cell origin
True
28
T/F Lymphoid neoplasms are often associated with immune abnormalities
True
29
T/F Non-Hodgkin lymphoma spreads in an orderly stepwise fashion, whereas most forms of Hodgkin lymphomas disseminate widely and somewhat unpredictably early in their course
False
Hodgkin lymphoma spreads in an orderly stepwise fashion, and most forms of NHL disseminate widely and unpredictably early in their course
30
the most common cancer of children
Acute Lymphoblastic Leukemia/Lymphoma (ALL)
31
T/F Peak incidence of B-ALL is in adolescence, the age when the thymus reaches maximum size
False, T-ALL
32
Most T-ALLs have mutations in ___ a gene that is essential for T-cell development
NOTCH1
33
a high fraction of B-ALLs have mutations affecting genes such as ___(4) , all of which are required for the proper differentiation of early hematopoietic precursors
PAX5, TCF3, ETV6, and RUNX1
34
Histochemical stains are helpful in distinguishing ALL from AML, that (in contrast to myeloblasts) lymphoblasts are myeloperoxidase (positive or negative?)
negative
35
_____ is a specialized DNA polymerase that is expressed only in pre-B and pre-T lymphoblasts and ihc staining for this is positive in 95% of cases of ALL
terminal deoxynucleotidyl transferase (TdT)
36
B-ALL lymphoblasts usually express the pan B-cell marker CD19 and the transcription factor PAX5 as well as CD10. However, in very immature B-ALLs, one of the 3 is negative.
CD10
37
in T-ALLs these usual T-cell anitgens are negative in more immature tumors (3)
CD3, CD4, and CD8
38
factors are associated with a worse prognosis in ALL (3)
1. <2 years of age
2. presentation in adolescence or adulthood
2. peripheral blood blasts greater than 100,000
39
factors are associated with a favorable prognosis in ALL (5)
1. age between 2 and 10 years
2. low white cell count
3. hyperdiploidy
4. trisomy of chromosome 4, 7, and 10
5. presence of t(12;21)
40
T/F The BCR-ABL protein in B-ALL with a t(9;22), has stronger tyrosine kinase activity than the form of BCR-ABL that is found in chronic myeloid leukemia
True
41
T/F Clinical presentations of ALL and AML vary widely
False
they are clinically very similar
42
The most common genetic anomalies in CLL/SLL are (4)
deletions of 13q14.3, 11q, and 17p and trisomy 12q
43
T/F. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) differ only in the degree of peripheral blood lymphocytosis
True
44
overexpression of the anti-apoptotic protein ______, is uniformly observed in CLL/SLL
BCL2
45
pathognomonic for CLL/SLL
proliferation centers
46
In this peripheral B-Cell neoplasm, lymph nodes are diffusely effaced by predominantly small lymphocytes 6 to 12 μm in diameter with round to slightly irregular nuclei, condensed chromatin, and scant cytoplasm.
CLL/SLL
47
In CLL/SLL the blood contains variable numbers of small round lymphocytes with scant cytoplasm. Some of these cells are usually disrupted in the process of making smears, producing so-called
smudge cells
48
CLL/SLL has a distinctive immunophenotype. The tumor cells express the pan B-cell markers CD19 and CD20, as well as _______(2)
CD23 and CD5
49
Transformation of CLL/SLL to diffuse large B-cell lymphoma (DLBCL) is called _____ syndrome
Richter syndome
50
Richter syndrome is often heralded by the development of a rapidly enlarging mass within a lymph node or the spleen. It is often associated with acquisition of new abnormalities involving the genes _____(2)
TP53 and MYC
51
Follicular lymphoma is strongly associated with chromosomal translocations involving
BCL2
52
hallmark translocation of folliulcar lymphoma which leads to overexpression of BCL2
t(14;18)
53
Two principal cell types present in varying proportions in follicular lymphoma
centrocytes
centroblasts
54
in follicular lymphoma large cells with open nuclear chromatin, several nucleoli, and modest amounts of cytoplasm, are referred to as
centroblasts
55
in follicular lymphoma small cells with irregular or cleaved nuclear contours and scant cytoplasm are referred to as
centrocytes
56
follicular lymphoma ihc:
CD20
CD10
BCL6
BCL2
CD5
CD20 +
CD10 +
BCL6 +
BCL2 +
CD5 -
57
T/F Follicular lymphoma is incurable
True
58
90% of follicular lymphomas have a mutation in
KMT2D
59
drives Warburg metabolism and rapid cell growth
MYC mutation
60
the most common form of NHL in adults
Diffuse large B-cell lymphoma (DLBCL)
61
One frequent pathogenic event in DLBCL is dysregulation of _____, a DNA-binding zinc-finger transcriptional repressor that is required for the formation of normal germinal centers
BCL6
62
T/F DLBCLs with MYC translocations have a worse prognosis
True
63
All forms of Burkitt lymphoma are associated with translocations of the ___ gene on chromosome ___
MYC gene on chromosome 8
64
MYC is a master transcriptional regulator that increases the expression of genes that are required for aerobic glycolysis called the ____ effect
Warburg effect
65
Essentially all endemic Burkitt lymphomas are latently infected with
EBV
66
This tumor exhibits a high mitotic index and contains numerous apoptotic cells, the nuclear remnants of which are phagocytosed by interspersed benign macrophages.These phagocytes have abundant clear cytoplasm, creating a characteristic “starry sky” pattern.
Burkitt lymphoma
67
category of burkitt lymphoma that often presents as a mass involving the mandible and shows an unusual predilection for involvement of abdominal viscera, particularly the kidneys, ovaries, and adrenal glands
endemic
68
category of burkitt lymphoma that often appears as a mass involving the ileocecum and peritoneum
sporadic
69
Virtually all mantle cell lymphomas have this translocation
t(11;14)
70
is over expressed in mantle cell lymphoma
cyclin D1
71
up-regulation of cyclin D1 in mantle cell lymphoma promotes ______ progression during the cell cycle
G1- to S-phase
72
NHL most likely to present with mucosal involvement of the small bowel or colon produces polyp-like lesions (lymphomatoid polyposis)
mantle cell lymphoma
73
Typically, the proliferation in this NHL consists of a homogeneous population of small lymphocytes with irregular to occasionally deeply clefted (cleaved) nuclear contours. Large cells resembling centroblasts and proliferation centers are absent
Mantle cell lymphoma
74
Mantle cell IHC
cyclin D1
CD20
CD5
CD23
cyclin D1 +
CD20 +
CD5 +
CD23 -
75
T/F mucosa-associated lymphoid tumors (or MALTomas) often arise within tissues involved by chronic inflammatory, remain localized for prolonged periods, and do not regress even if the inciting agent is eradicated
False
first 2 descriptions are true but the last is false. They may regress if the inciting agent (e.g., H. pylori) is eradicated.
76
hairy cell leukemia is associated most commonly with this point mutation
BRAF V600E
77
is the most common clinical and sometimes the only abnormal physical finding in hairy cell leukemia
splenomegaly
78
most common indolent lymphoma of adults
follicular lymphoma
79
This uncommon entity is defined by the presence of rearrangements in the ALK gene on chromosome 2p23
Anaplastic Large-Cell Lymphoma (ALK Positive)
80
has a worse prognosis
ALK-/ALK+ anaplastic large cell lymphoma
ALK-
81
This neoplasm of CD4+ T cells is observed only in adults infected by HTLV-1
Adult T-Cell Leukemia/Lymphoma
82
are different manifestations of a tumor of CD4+ helper T cells that home to the skin (2)
Mycosis fungoides and Sézary syndrome
83
is a variant of CD4+ helper T cell tumors in which skin involvement is manifested as a generalized exfoliative erythroderma
Sézary syndrome
84
Approximately 30% to 40% of large granular lymphocytic leukemias have acquired mutations in the transcription factor
STAT3
85
T-cell variants of large granular lymphocytic leukemias express CD3 on their surfaces, whereas NK-cell variants lack surface CD3 and express NK markers such as
CD56
86
some with this syndrome, characterized by the triad of rheumatoid arthritis, splenomegaly, and neutropenia, have large granular lymphocytic leukemias as an underlying cause
Felty syndrome
87
white blood cell neoplasm which most frequently presents as a destructive nasopharyngeal mass. The tumor cell infiltrate typically surrounds and invades small vessels, leading to extensive ischemic necrosis. In touch preparations, large azurophilic granules are seen in the cytoplasm of the tumor cells that resemble those found in normal NK cells.
Extranodal NK/T-Cell Lymphoma
88
Extranodal NK/T-cell lymphoma is highly associated with this virus
EBV
89
surface protein that serves as the B-cell EBV receptor
CD21
90
In most patients with plasma cell tumors, the level of free light chains is elevated and markedly skewed toward one light chain (e.g., κ) at the expense of the second (e.g., λ). Because free light chains are small in size, they are also excreted in the urine, where they are referred to as
Bence Jones proteins
91
the most important plasma cell neoplasm, usually presents as tumor masses scattered throughout the skeletal system associated with lytic bone lesions, hypercalcemia, renal failure, and acquired immune abnormalities
Multiple myeloma (plasma cell myeloma)
92
plasma cell neoplasm that presents as a single mass in bone or soft tissue
Solitary myeloma (plasmacytoma)
93
plasma cell neoplasm defined by a lack of symptoms and a high plasma M component >3g/dL
Smoldering myeloma
94
is a syndrome in which high levels of IgM lead to symptoms related to hyperviscosity of the blood. It occurs in older adults, most commonly in association with lymphoplasmacytic lymphoma
Waldenström macroglobulinemia
95
plasma cell disorder wherein patients have no signs or symptoms but have small to moderately large M components <3g/dL in their blood.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
96
Virtually all cases of lymphoplasmacytic lymphoma are associated with acquired mutations in
MYD88
97
In this B-cell neoplasm, the marrow contains an infiltrate of lymphocytes, plasma cells, and plasmacytoid lymphocytes in varying proportions, often accompanied by mast cell hyperplasia
Lymphoplasmacytic lymphoma
98
Multiple myeloma is genetically heterogeneous and is associated with frequent rearrangements involving the
IGH locus
99
Morphologically, the distinctive feature of Hodgkin lymphoma is the presence of neoplastic giant cells called
Reed-Sternberg cells
100
T/F Hodgkin lymphoma arises in a single node or chain of nodes and spreads first to anatomically contiguous lymphoid tissues
true
101
first human cancer to be successfully treated with radiation therapy and chemotherapy
Hodgkin lymphoma
102
out of the 5 subtypes of Hodgin lymphoma, 4 make up the “classic” forms namely
1. Nodular sclerosis
2. Mixed cellularity
3. Lymphocyte-rich
4. Lymphocyte depletion
103
In the hodgkin lymphoma subtype, lymphocyte predominance, the Reed-Sternberg cells have a (B/T?)-cell immunophenotype that differs from that of the classic types.
B
104
T/F Due to their B-cell origin, the Reed-Sternberg cells of classic Hodgkin lymphoma express most B-cell– specific genes, including the Ig genes.
False, despite their B-cell origin the classic forms do not express B-cell specific genes
105
common event in classic Hodgkin lymphoma and turns on genes that are believed to promote the growth and survival of Reed-Sternberg cells
Activation of the transcription factor NF-κB
106
Several Reed-Sternberg cell variants are also recognized namely (3)
mononuclear variant
lacunar variant
lymphohistiocytic variant, L&H variant (popcorn cell)
107
most common form of Hodgkin lymphoma. It is characterized by deposition of collagen in bands that divide involved lymph nodes into circumscribed nodules
Nodular Sclerosis Type
108
Reed-Sternberg cell variant found characteristically in the nodular sclerosis subtype
lacunar variant
109
characteristic immunophenotype of Reed-Sternberg cells in the 4 classic Hodgkin lymphoma subtypes
PAX5
CD15
CD30
CD20
LCA
PAX5 +
CD15 +
CD30 +
CD20 -
LCA -
110
Reed-Sternberg cells in HL of the mixed cellularity subtype are infected with ____ in about 70% of cases
EBV
111
least common subtype of Hodgkin lymphoma
lymphocyte depletion type
112
The Reed-Sternberg cells of the HL lymphocyte depletion subtype are infected with _____ in over 90% of cases
EBV
113
Reed-Sternberg cell variant commonly found in the nodular lymphocyte predominance subtype
L&H variant (popcorn cell)
114
Reed-Sternberg cells of L&H variant found in nodular lymphocyte predominance subtype of hodgkin lymphoma express
CD20
BCL6
CD15
CD30
CD20 +
BCL6 +
CD15 -
CD30 -
115
The spread of Hodgkin lymphoma is remarkably stereotypic (5)
nodal
splenic
hepatic
bone marrow
other tissues
116
most important prognostic variable in HL
tumor stage
117
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann Arbor Classification)
1
2
3
4
1. Involvement of a single lymph node region (I) or a single extralymphatic organ or site (IE)
2. Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or localized involvement of an extralymphatic organ or site (IIE)
3. Involvement of lymph node regions on both sides of the diaphragm without (III) or with (IIIE) localized involvement of an extralymphatic organ or site
4. Diffuse involvement of one or more extralymphatic organs or sites with or without lymphatic involvement
118
Pathogenic mechanism:
Burkitt lymphoma
Follicular lymphoma
Hodgkin lymphoma
Mantle cell lymphoma
Acute lymphoblastic leukemia
Marginal zone lymphoma
Burkitt lymphoma
dysregulation of MYC
Follicular lymphoma
dysregulation of BCL2
Hodgkin lymphoma
PD-1 ligand gene amplification
Mantle cell lymphoma
loss of cell cycle control (cyclin D1 rearrangements)
Acute lymphoblastic leukemia
loss of the CDKN2A
Marginal zone lymphoma
chronic immune stimulation
119
Three broad, major categories of myeloid neoplasms
Acute myeloid leukemias
Myelodysplastic syndromes
Myeloproliferative neoplasms
120
a tumor of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow
Acute myeloid leukemia (AML)
121
distinctive subtype of AML associated with the t(15;17) that create the chimeric protein PML-RARa
acute promyelocytic leukemia
122
the two most common chromosomal rearrangements in AML and the polypeptides they disrupt
t(8;21) - RUNX1
inv(16) - CBFB
123
distinctive needle-like azurophilic granules, present in many cases; they are particularly numerous in AML with the t(15;17) (acute promyelocytic leukemia)
auer rods
124
The diagnosis of AML is based on the presence of at least __% myeloid blasts in the bone marrow.
20%
125
AML immunophenotype
CD34
CD64
CD33
CD15
CD34 + marker for multipotent stem cells
CD64 - marker for mature myeloid cells
CD33 + marker for immature myeloid cells
CD15 +/- marker for more mature myeloid cells
126
AML arising de novo in younger adults is commonly associated with balanced chromosomal translocations, particularly (3)
t(8;21), inv(16), and t(15;17)
127
AML following MDS or exposure to DNA-damaging agents (such as chemotherapy or radiation therapy) often has deletions or monosomies involving (2)
chromosome 5 and 7
128
AML following MDS or exposure to DNA-damaging agents (such as chemotherapy or radiation therapy) usually lack chromosomal translocations EXCEPT for those treated with ___
topoisomerase II inhibitors, which are strongly associated with translocations involving the KTM2A gene
129
AML subtype with the best prognosis, being curable in more than 90% of patients
AML with t(15;17); RARa fusion gene
130
refers to a group of clonal stem cell disorders characterized by maturation defects that are associated with ineffective hematopoiesis and a high risk of transformation to AML
myelodysplastic syndrome
131
All forms of MDS can transform to AML, but transformation occurs with highest frequency and most rapidly in
t-MDS or MDS secondary to previous genotoxic drug or radiation therapy
132
clonal stem cell disorder wherein the most characteristic finding is disordered (dysplastic) differentiation affecting the erythroid, granulocytic, monocytic, and megakaryocytic lineages to varying degrees
myelodysplastic syndrome
133
_____ are neutrophils with only two nuclear lobes are often seen in MDS
Pseudo–Pelger-Hüet cells
134
is distinguished from other myeloproliferative neoplasms by the presence of a chimeric BCR-ABL gene derived from portions of the BCR gene on chromosome 22 and the ABL gene on chromosome 9
Chronic Myeloid Leukemia (CML)
135
In more than 90% of cases of CML, BCR-ABL is created by a reciprocal (9;22)(q34;q11) translocation, the so-called ____
Philadelphia chromosome
136
characterized by increased marrow production of red cells, granulocytes, and platelets (panmyelosis), but it is the increase in red cells that is responsible for most of the clinical symptoms
Polycythemia vera (PCV)
137
In PCV, the transformed progenitor cells have markedly decreased requirements for erythropoietin and other hematopoietic growth factors due to activating mutations in the tyrosine kinase
JAK2
138
pathway which lies downstream of multiple hematopoietic growth factor receptors, including the erythropoietin receptor
JAK/STAT pathway
139
serum erythropoietin levels in PCV are low/high?
low
140
serum erythropoietin levels in secondary polycythemia are low/high?
high
141
substitution that occurs in JAK2 mutation
valine to phenylalanine
142
most common mutation in Langerhans cell histiocytosis
BRAFV600E
143
substitution in BRAFV600E
valine to glutamate
144
______ in the cytoplasm is characteristic in Langerhans cell histiocytosis. They are pentalamiar tubules, often with a dilated terminal end producing a tennis racket–like appearance which contain the protein langerin
Birbeck granules
